Tyrosine kinase is an enzyme which phosphorylates tyrosine residues in substrate proteins, and is known to play an important role in an intracellular signal transduction system concerning cellular differentiation and proliferation. Especially, it is known that a growth factor receptor tyrosine kinase (hereinafter receptor tyrosine kinase) such as HER2 (also called as ErbB2 or Neu) and EGF receptor etc. are considerably involved in cancer development, and their activities are increased in a variety of human cancers (Non-Patent Document 1, Non-Patent Document 2 and Non-Patent Document 3).
Also it is known that co-expression of EGF receptor and HER2 further promotes canceration by EGF receptor alone (Non-Patent Document 4) and a dual inhibitor that inhibits tyrosine kinase of both EGF receptor and HER2 is advantageous in having superior therapeutic effect in wider range of disease by synergistic effect of dual inhibition when compared with a EGF receptor or a HER2 selective inhibitor.
According to Patent Document 1, a quinazoline derivative represented by the following Formula:
has dual inhibitory activity for EGF receptor and HER2, and is useful as a therapeutic and/or prophylactic agent for cancer. The following compound (VIII-102):
in a free base form is disclosed in an Example thereof, but neither an acid addition salt nor a solvate thereof is specifically disclosed. Also, crystals thereof are not specifically disclosed.
A method for producing a quinazoline derivative represented by Formula (VI′):
is described in Patent Document 2. Also, the following compound (VI-15):
in a free base form is disclosed in an Example thereof, but neither an acid addition salt nor a solvate thereof is specifically disclosed. Also, crystals thereof are not specifically disclosed.
Patent Documents 3 and 4 disclose hydrate crystals and anhydride crystals of Lapatinib ditosylate (ditosylate salt of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine) that has a dual inhibitory action for EGF receptor and HER2, and is represented by the following Formula.
Also, Patent Document 5 discloses anhydride crystals of a free base of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine.
In drug delivery, a crystal form that has useful and excellent chemical and/or physical properties is desired.